It was demonstrated previously that macrophages specifically interact with a distinct B cell subpopulation which is characterized as Lyb5+. Current experiments have demonstrated that Lyb5- B cells can be stimulated by the mitogen LPS. To gain further insights into the activation requirement of B cells which comprise the Lyb5- B cell subpopulation, the ability of lipoprotein free (phenol extracted) and lipoprotein rich (butanol extracted) LPS to stimulate Lyb5- B cells was examined. It was shown that butanol extracted LPS stimulates-all Lyb5- cells. In contrast, phenol extracted LPS stimulates only a specific Lyb5- B cell subset which is present in normal mice, but which is absent in xid mice. Thus, these results define a new B cell subpopulation which is Lyb5-, appears early in ontogeny, and is absent in mutant xid mice.